Thrombin causes pseudopod detachment via a pathway involving cytosolic phospholipase A(2) and 12/15-lipoxygenase products

Thrombin causes rapid pseudopod detachment and shortening in Dunning rat pr ostatic carcinoma (MAT-Lu) cells. As seen by interference reflection micros copy and by immunofluorescence analysis; with antibodies to paxillin and ta lin, the primary event is disassembly of adhesion sites. Biochemically, thr ombin is a potent activator of cytosolic phospholipase A, and increases eic osanoid production in these cells, The pseudopod effects are blocked by lip oxygenase (but not cyclooxygenase) inhibitors. Arachidonic acid and 12(S)hy droxyeicosatetraenoic acid or 15(S)-hydroxyeicosatetraenoic acid mimic the thrombin effect. We conclude that in certain cancer cells, thrombin is a ps eudopod repellent that exerts its effect via a cascade involving cytosolic phospholipase A(2), 12/ 15-lipoxygenase, and 12(S)- and/or 15(S)-hydroxyeic osatetraenoic acid.